Fatigue is the most common post-treatment problem among cancer survivors, affecting a third or more of long-term survivors. Persistent fatigue in survivors may be related in part to overactivation of the inflammatory network; the immune activation that is secondary to the tissue destruction and associated inflammation from many cancer therapies may leave patients vulnerable to the behavioral consequences of proinflammatory cytokines, including fatigue. What is more, a cancer diagnosis and cancer treatments can be quite stressful, and stress and depression can directly enhance the production of proinflammatory cytokines. Fatigue has been well-studied in breast cancer survivors, but far less is known about fatigue in other cancer survivor populations. Furthermore, although several lines of evidence suggest that inflammation plays a significant role in cancer-related fatigue, the data are limited, and longitudinal data in survivors are almost nonexistent. Moreover, the extent to which the incidence and prevalence of fatigue among cancer survivors differs from comparable adults without a cancer history remains an important question; similarly, whether there are differences in inflammation between cancer survivors and adults without a cancer history is unknown. This project provides the opportunity to examine mechanistic connections among fatigue, depression, NF-B activation, health behaviors, and proinflammatory cytokines both cross-sectionally and longitudinally, with initial data on each of these key dimensions collected before cancer treatment, as well as 6 months, 18 months, and 30 months after completion of primary treatment. Subjects will be stage I-IIIA breast cancer survivors, stage I- IIIC colon cancer survivors, and men and women who had a benign diagnosis following an initial abnormal test for breast or colon cancer. The proposed project would provide the first prospective study of inflammation, depression, and fatigue from pretreatment through survivorship in two groups of cancer survivors, as well as a noncancer comparison group. Specific Aims: (1) To assess the association between inflammation and fatigue cross-sectionally at each of the time points, as well as the extent to which higher levels of inflammatory markers at baseline predict subsequent fatigue; to evaluate these relationships in breast and colon cancer patients, as well as noncancer controls, and to compare the magnitude of both cross-sectional and longitudinal associations across the three groups. (2) To evaluate relationships between past or current syndromal depression and/or depressive symptoms with inflammatory markers, NF-B activation, and fatigue, as well as their association with subsequent inflammation and fatigue. (3) To appraise the relative impact of health-related behaviors (sleep, pain, physical activity, n-6:n-3 dietary fatty acids, central adiposity, and chronic health conditions) as correlates and predictors of syndromal depression and depressive symptoms, inflammatory markers, and fatigue. Fatigue is the most common post-treatment problem among cancer survivors, affecting a third or more of long- term survivors. Several lines of evidence suggest that immune system activation plays a significant role in cancer-related fatigue; however, the data are limited and longitudinal data as well as data comparing survivors to noncancer controls are almost nonexistent. The proposed project would provide the first prospective study of inflammation, depression, fatigue, and health-related behaviors from pretreatment through survivorship in two groups of cancer survivors, as well as a noncancer comparison group.